APPLICANT'S ABSTRACT: It is estimated that there are now about 6 million regular users of smokeless tobacco (snuff or chewing tobacco) in the United States. The rate of consumption of smokeless tobacco (SLT) is of particular concern due to the potential for addiction and physical dependence on SLT. Negative health consequences are also associated with the use of smokeless tobacco. Although many SLT users report wanting to quit, few well-controlled studies have been conducted examining treatments for SLT users. Of the previous studies, including our own that examined the effects of nicotine gum vs. placebo gum, the results have been dismal. We are asking for continuation of funds for the continuation of a current treatment study that examines the effects of primary and secondary reinforcement properties of smokeless tobacco on craving, withdrawal symptoms and treatment outcome. This study will involve a 2 x 2 design where subjects (N=400, 100 in each treatment condition) have been assigned randomly and in a semi-double blind fashion to one of four treatments: transdermal nicotine system (TNS; primary reinforcement) versus placebo; and mint snuff (non-nicotine product with secondary reinforcement properties) versus no-mint snuff. Also this study carefully and intensively examines factors associated with lapse and relapse situations and coping skills used to circumvent lapse or relapse in a random sample of subjects who are abstinent at the end of treatment. Continuation for funds for this study are requested since, upon the recommendations of the IRG, we increased our sample size (from 200 to 400) and extended the follow-up from 6 to 12 months. We made this modification with no increase in funding or time. The results from this study will provide a greater understanding of factors associated with dependence on SLT, an effective method for the treatment of SLT users and a greater understanding of factors which lead to or prevent relapse. This grant proposal will also run eight human laboratory experiments that will focus on factors that facilitate and minimize SLT use. A laboratory model will be systematically developed in which abstinent SLT users are exposed to smokeless tobacco-related stimuli and them required to work for tokens that can be exchanged for money or specific amounts of SLT. Factors that will be examined and considered to facilitate smokeless tobacco use will include longer lengths of abstinence, exposure to a priming dose of smokeless tobacco, use of alcohol, and food restriction. On the other hand, factors that will be examined and thought to minimize SLT use include TNS, nicotine gum and the availability of alternative reinforcers. These experiments will provide a laboratory model that will allow for a more systematic and efficient observation of factors associated with relapse and the manipulation of variables that may be effective in treatment.